Assessing Congestion in HF:

Natriuretic Peptides

Michael Felker, MD, MHS, FACC, FAHA

Professor of Medicine

Chief, Heart Failure Section

Duke University School of Medicine

Vicious Cycle of Congestion in AHF

Worsening heart failure

Elevated LVEDP

Increased wall stress

Myocardial Oxygen demand

Myocardial ischemia

Increased functional MR

CONGESTION

“If you wish to converse with me, define your terms.”

Voltaire

Congestion

• All agree that it is important

• All agree that addressing it is key to success

• What is it exactly?

– Clinical congestion (rales, JVP, edema)?

– Hemodynamic congestion (elevated filling pressures)?

– Something else (fluid loss, body weight change, NP’s)?

Pharmacologic Actions of hBNP

Hemodynamic

(balanced vasodilation)

veins

arteries

coronary arteries

Neurohumoral

aldosterone

endothelin

norepinephrine

Renal

diuresis

natriuresis

GFR

D R I

M K R G

S S S

S G L G

F C

C S S

G S G Q V M

K V L R R

H

K P S

Cardiac

lusitropic

antifibrotic

anti-remodeling

BNP Correlates (Loosely) with LV Filling Pressures

Kazanegra J, Cardiac Failure 2001

PA

W (

mm

Hg

)

Hours

BN

P (p

g/m

l)

15

17

19

21

23

25

27

29

31

33

baseline 4 8 12 16 20 24 600

700

800

900

1000

1100

1200

1300

PAW BNP

*Pulmonary artery wedge.

BNP Reflects Ventricular Wall Stress

Iwananga, JACC

2006

Natriuretic Peptides Represent a “Myocyte

Level” View of Congestion

Help!

Maisel AS et al. N Engl J Med. 2002;347:161-167.

1.0

0.8

0.6

0.4

0.2

0.0

0.0 0.2 0.4 0.6 0.8 1.0

1-Specificity

Sen

sit

ivit

y

Final Diagnosis

Heart Failure

Final Diagnosis

NOT Heart Failure

BNP 100 pg/mL

“Test positive”

673 227

BNP <100 pg/mL

“Test negative”

71

Sensitivity

=90%

615

Specificity

=73%

Positive

predictive

value=75%

Negative

predictive

value=90%

BNP=50 pg/mL

BNP=80 pg/mL

BNP=100 pg/mL

BNP=150 pg/mL

BNP=125 pg/mL

Natriuretic Peptides for Diagnosis

Optimal cut-off point determined @ 100 pg/mL

Maisel AS et al. N Engl J Med. 2002;347:161-167.

Natriuretic Peptides and Prognosis in Chronic HF:

Data from Val-HeFT

Anand, I. et al, Circ 2003

Predischarge BNP Is Strong Predictor of Post-

Discharge Events

0

25

50

75

100

0 30 60 90 120 150 180

De

ath

or

Re

ad

mis

sio

n, %

Follow-up, Days

Hazard Ratios

15.2

5.1

1

p<.0001

p<.0001

BNP >700 ng/L*

(n = 41, events = 38)

BNP 350-700 ng/L*

(n = 50, events = 30)

BNP <350 ng/L*

(n = 111, events = 18)

Logeart D, et al. J Am Coll Cardiol. 2004;43:635-641.

Change in NTproBNP and Outcomes

Masson, JACC 2008

Kociol R et al, Circ HF 2013

Biomarker Guided Therapy and All-Cause Mortality:

Meta-Analysis

Combined

BATTLESCARRED

STARS-BNP

STARBRITE

Troughton

TIME-CHF

PRIMA

Felker GM. Am Heart J 2009

N = 1627

Adjusted HR = 0.69 (0.55-0.86)

High Risk Systolic HF Patient

LVEF ≤ 40 within 12 months

HF event within 12 mos (HF hosp, ER visit, or outpt IV diuretic)

NTproBNP > 2000 pg/mL within last 30 days

Usual Care

N= 550

Primary endpoint: Time to CV death or first HF hospitalization

Secondary Endpoints: All-cause mortality

Total days alive and out of hospital during follow-up

CV mortality or CV hospitalization

Safety

Health related quality of life

Resource utilization, costs, cost-effectiveness

Biomarker Guided

NTproBNP < 1000 pg/mL

N=550

Follow up: 2 wks, 6 wks, 3 months, then Q3 month for 12-24 mos

Screening

Randomization

Follow-up

Endpoints

Additional 2 week follow up after changes in therapy

Ambulatory/Outpatient

In ambulatory patients with dyspnea, measurement of

BNP or N-terminal pro-B-type natriuretic peptide (NT-

proBNP) is useful to support clinical decision making

regarding the diagnosis of HF, especially in the setting of

clinical uncertainty.

Measurement of BNP or NT-proBNP is useful for

establishing prognosis or disease severity in chronic HF.

I IIa IIb III

I IIa IIb III

Hospitalized/Acute

Measurement of BNP or NT-proBNP is useful to support

clinical judgment for the diagnosis of acutely

decompensated HF, especially in the setting of

uncertainty for the diagnosis.

Measurement of BNP or NT-proBNP and/or cardiac

troponin is useful for establishing prognosis or disease

severity in acutely decompensated HF.

I IIa IIb III

I IIa IIb III

Advantages of Natriuretic Peptides as

Measures of Congestion

• Quantitative

• Reproducible across time and across providers

• Does not require high level of expertise

• Non-invasive

• Cheap (relatively)

• Supported by guidelines with highest level of

recommendation

Biomarkers Always Augment Clinical Judgment

• Impacted by

– Age

– Gender

– Renal function

– Atrial fibrillation

– Obesity

– HFpEF vs. HFrEF

Greater Decongestion = Better Outcomes

Kociol et al, Circ HF 2013

• Drop in NT-

proBNP

• Change in

weight

• Net fluid loss

Conclusions

• Natriuretic peptides represent a quantitative,

reproducible assessment of myocyte wall stress

– Best marker for making diagnosis of HF

– Correlate with symptoms

– Correlate with outcomes

– Change with favorable change in clinical course

– Failure to improve with treatment identifies very high risk

patients

– ? Potential target for adjusting therapy